Electronic control of drug delivery system

ABSTRACT

In an exemplary embodiment, a drug delivery device for driving an electrotransport current through a body surface of a user is provided. The device includes a patch with two electrodes and one or more reservoirs storing a therapeutic agent. The one or more reservoirs release the therapeutic agent into the body surface of the user when the reservoirs are positioned over the electrodes to form an electrical path for the electrotransport current. The device includes a controller which controls a controllable power supply to drive the electrotransport current through the body surface of the user in a predetermined profile.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 61/141,377, filed on Dec. 30, 2008, and titled “Electronic ControlOf Drug Delivery System”, which is incorporated herein by reference inits entirety.

BACKGROUND

Drug delivery is the method or process of delivering a pharmaceuticaldrug or agent to achieve a therapeutic effect in a user (defined ashumans or animals). Drug delivery technologies are intended to controlor modify drug release profiles for the benefit of improving productefficacy and patient convenience and compliance. Common methods ofparenteral delivery include the following routes: intravenous,intramuscular, subcutaneous, intradermal, transdermal, inhalational,etc.

Drug delivery technologies may include the use of electronic circuits tocontrol the duration of administration or the dose (amount) of apharmaceutical drug or agent. Iontophoresis is an example of a drugdelivery technology that implements electronic control over theadministration of a drug. Iontophoresis utilizes an electrical currentto transport a drug or agent transdermally, i.e. through the user'sskin, in a safe and effective manner.

SUMMARY

Exemplary embodiments may provide methods, systems and apparatuses for adrug delivery system or device which implements electronic control overthe release of a pharmaceutical drug or agent. The terms “drug deliverysystem” and “device” can be used interchangeably in the context of thepresent invention. In exemplary embodiments, the electronic control maycontrol an electrotransport current which transdermally delivers anagent to a user. Exemplary embodiments may achieve a desired profile intime of the agent in the user's body by controlling a profile in time ofthe electrotransport current.

Exemplary embodiments may control the electrotransport current using alinear regulator or any type of a switching regulator.

In an exemplary embodiment, the electrotransport current may becontrolled using pulse width modulation (PWM), e.g. by adjusting theduty cycle of a PWM power supply. Exemplary embodiments may generateinterrupts at regular intervals, and perform current correction upon thegeneration of each interrupt. Exemplary embodiments may detect theelectrotransport current flowing through the user's skin, and compare itto a dynamic current value representative of the target current. Thetarget current may be based on the desired current profile. Based on acomparison of the electrotransport current and the dynamic valuerepresentative of the target current, exemplary embodiments mayincrease, decrease or retain the current duty cycle of the PWM powersupply.

Exemplary embodiments may also include methods and apparatuses used forthe testing of the electronic connection of drug delivery devices (i.e.,iontophoretic drug delivery systems as taught herein). Such exemplaryapparatuses may include an electrode patch continuity tester that isadapted for use in the testing and verification of the connections ofthe iontophoretic drug delivery system.

Exemplary methods may also include methods for the testing andverification of the electronic connections of the iontophoretic drugdelivery system.

Exemplary methods may also include methods for testing, measuring orotherwise quantifying the capacity of the electrode of an iontophoreticdrug delivery system, as described herein, to deliver a drug.

In one exemplary embodiment, a method of driving an electrotransportcurrent through an animal body surface using a pulse width modulation(PWM) controller is provided. The method includes driving theelectrotransport current through the animal body surface using a PWMpower supply. The method also includes generating one or more interruptsat predetermined intervals using a timer, and turning off the PWM powersupply using the PWM controller when the one or more interrupts aregenerated. The method further includes controlling a duty cycle of thePWM power supply using the PWM controller at least based on a presentvalue of the electrotransport current and a dynamic value representativeof a target electrotransport current.

In a further exemplary embodiment, a drug delivery device for driving anelectrotransport current through an animal body surface is provided. Thedevice includes a first electrode, a second electrode, a controller(e.g. a programmable processor) configurable, programmable, or both tocontrol an electrical current flowing between the first and secondelectrodes, a first conductive reservoir holding a first conductivemedium and a therapeutic drug or agent to be positioned over the firstelectrode, a second conductive reservoir holding a second conductivemedium and optionally an ion source to be positioned over the secondelectrode to form an electrical path for the electrical current. Thedevice also includes a pulse width modulation (PWM) power supply forapplying an output voltage across the animal body surface, and drivingthe electrotransport current through the animal body surface. The devicefurther includes a controller to drive the electrotransport currentthrough the animal body surface in a predetermined profile. Thecontroller has a current monitor, a voltage monitor and a voltageregulator for performing an output voltage correction to adjust theelectrotransport current.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments will be described below relative to the followingdrawings in which like reference characters refer to the same partsthroughout the different views.

FIG. 1 depicts a top view of an exemplary self-contained pre-packagediontophoretic drug delivery system;

FIG. 2 depicts a side view of the exemplary iontophoretic drug deliverysystem depicted in FIG. 1;

FIG. 3 depicts a cross-sectional side view of a portion of an exemplaryiontophoretic drug delivery system that includes a first electrode, asecond electrode and a controller;

FIG. 4 depicts an exploded perspective view of the portion depicted inFIG. 3;

FIGS. 5-8 depict exemplary current profiles achievable by an exemplarycontroller of an exemplary drug delivery system taught herein;

FIG. 9 depicts a general block diagram of an exemplary electroniccircuit for controlling an exemplary drug delivery system taught herein;

FIG. 10 depicts a schematic of an exemplary electronic circuit forcontrolling an exemplary drug delivery system taught herein;

FIG. 11 depicts a flow diagram of an exemplary control loop implementedby the exemplary electronic circuit depicted in FIG. 10;

FIG. 12 depicts a flow diagram of an exemplary method of testing theelectronic connections of the device such as that depicted in FIG. 1;and

FIG. 13 depicts a flow diagram of an exemplary method of testing thecapacity of a device, such as that depicted in FIG. 1, to deliver atarget drug quantity.

DETAILED DESCRIPTION

Exemplary embodiments may provide methods, systems and apparatuses for adrug delivery system which implements electronic control over therelease of a pharmaceutical drug or agent in a user. In exemplaryembodiments, the electronic control may control an electrotransportcurrent which transdermally delivers a drug to a user. Exemplaryembodiments may achieve a desired profile in time and dosage of the drugin the user's body (e.g., a drug delivery profile and/or a plasmaconcentration profile) by controlling a profile in time of theelectrotransport current.

Exemplary embodiments may control the electrotransport current byemploying a power supply which is controllable using a linear regulatoror any type of a switching regulator. In an exemplary embodiment, thepower supply may be controllable by pulse width modulation (PWM). Suchcontrol of the drug delivery profile optimizes efficacy and safety ofthe drug, and allows automatic compliance of the drug regimen withoutthe user having to monitor or alter the settings of the system duringdosing.

Exemplary embodiments may regulate the electrotransport current byadjusting the duty cycle of the PWM power supply. Exemplary embodimentsmay generate interrupts at intervals, and perform current correction, ifnecessary, upon the generation of each interrupt. Exemplary embodimentsmay detect the electrotransport current flowing through the user's skinand compare it to a dynamic value representative of the target current.The target current may be based on the desired current profile. Based ona comparison of the electrotransport current and the dynamic valuerepresentative of the target current value, exemplary embodiments mayincrease, decrease or retain the current duty cycle of the PWM powersupply.

Before continuing with the remainder of the description, it may behelpful to first define some terms as used through out the specificationand claims.

The terms “user” and “subject” are used interchangeably herein, andinclude animals (e.g., mammals, e.g., cats, dogs, horses, pigs, cows,sheep, rodents, rabbits, squirrels, bears, and primates (e g ,chimpanzees, gorillas, and humans)) which may be treatable by themethods, systems and apparatuses of the present invention.

The term “drug” or “agent” includes any drug or agent which is capableof being administered in a therapeutically effective amount to a useremploying the devices of the present invention. The present inventioncan be used to administer agents of different molecular sizes andcharges. As used herein, a drug or agent may be a drug or otherbiologically active agent.

As used herein, the term “drug” and “therapeutic drug” are usedinterchangeably.

As used herein, the term “agent” and “therapeutic agent” are usedinterchangeably.

The term “drug delivery system” includes any system controlled by anelectronic circuit to deliver a drug or an agent in a therapeuticallyeffective manner. Examples of a drug delivery system include, but arenot limited to, an iontophoretic system, an intravenous (IV) drip, aninternal or external pump, an injected drug or agent, and an inhaleddrug or agent. As used herein, the terms “system” and “device” areinterchangeable.

As used herein, the term “computer readable media” refers to media thatmay store information or code, for example, magnetic discs, opticaldiscs, and memory devices (e.g., flash memory devices, static RAM (SRAM)devices, dynamic RAM (DRAM) devices, or other memory devices).

Certain exemplary embodiments are described herein to provide an overallunderstanding of the principles of the structure, function, manufacture,and use of the methods, systems and apparatuses disclosed herein. One ormore examples of these embodiments are illustrated in the accompanyingdrawings. The methods, systems and apparatuses specifically describedherein and illustrated in the accompanying drawings are non-limitingexemplary embodiments, and the scope of the present invention is definedsolely by the claims. The features illustrated or described inconnection with one exemplary embodiment may be combined with thefeatures of other embodiments. Such modifications and variations areintended to be included within the scope of the present invention.

FIGS. 1 and 2 depict an exemplary embodiment of a drug delivery system10 which uses iontophoresis to transdermally deliver a drug to a user.Iontophoresis is a method of applying a current to a user's skin toadminister an agent to the user's body through the skin of the user. Thedrug delivery system 10 of FIGS. 1 and 2 may be packaged as a patchwhich may be applied to the skin of the user and removed after the drughas been delivered. Some thicknesses in FIG. 2 are exaggerated forillustrative purposes.

As depicted by the cross-sectional side view of FIG. 2, the drugdelivery system 10 may include a first electrode 12 and a secondelectrode 14. In an exemplary embodiment, the electrodes 12 and 14 maybe round, circular, oval or any other geometrically suitable shape, orcoated wires. In a further exemplary embodiment, the wires may be coatedwith zinc or silver and/or silver/silver chloride.

In an exemplary embodiment, the electrodes 12 and 14 may furthercomprise a polyester film. One suitable polyester film is abiaxially-oriented polyethylene terephthalate polyester film sold underthe trademark Mylar®. Mylar® is an advantageous material because of itsthinness and flexibility. The polyester film of the electrodes 12 and 14may be screen-printed or etched on such films with conductive inkincluding silver/silver chloride. The polyester film may further includea dielectric coating to provide electrical insulation. In an exemplaryembodiment, the electrodes 12 and 14 may be affixed to the body of auser using fixing tape. In a further embodiment, components, likemicroprocessors and batteries, may be affixed directly onto thepolyester film with glue, conductive glue, solder, or tabs. In anotherexemplary embodiment, the electrodes 12 and 14 may comprise a polyimidefilm such as Kapton® polyimide film.

The drug delivery system 10 may include an exemplary control circuit 16that includes a microcontroller 150 programmed to control a current flowbetween the first electrode 12 and the second electrode 14. The controlcircuit 16 may include an on/off switch, such as a dome switch. In anexemplary embodiment, the microcontroller 150 may control theelectrotransport current by controlling a power supply using a linearregulator. In another exemplary embodiment, the microcontroller 150 maycontrol the power supply using any type of a switching regulator, e.g.pulse width modulation (PWM), pulse frequency modulation (PFM), etc. Anexemplary embodiment of the microcontroller 150 is discussed below inrelation to FIG. 11.

In an exemplary embodiment, the control circuit 16 may be separable fromthe first and second electrodes 12 and 14. In this embodiment, theelectrodes may be disposed after use and the control circuit 16 may bere-used. In another exemplary embodiment, the control circuit 16 may beintegrally attached to the electrodes.

The drug delivery system 10 may also include a first conductivereservoir 30 holding a first conductive medium and a first therapeuticdrug or agent and a second conductive reservoir 32 holding a secondconductive medium that may contain a second therapeutic drug or agent.In use, current supplied to the first electrode 12 delivers the firsttherapeutic drug or agent from the first conductive reservoir 30 througha portion of the user's skin in contact with the first conductivereservoir 30. Current returns to the second electrode 14 through aportion of the user's skin in contact with the second conductivereservoir 32. The second therapeutic drug or agent may have a chargeopposite that of the first therapeutic drug or agent. Foam rings may beused to hold the conductive drug reservoirs in place. The foam rings mayfurther keep the anode and cathode of the electrodes separated.

A first removable barrier 34 may form a first barrier seal removablydisposed between the first electrode 12 and the first conductivereservoir 30. A second removable barrier 36 may form a second barrierseal removably disposed between the second electrode 14 and the secondconductive reservoir 32. Alternatively, the first removable barrier 34may form both the first barrier seal and a second barrier seal removablydisposed between the second electrode 14 and the second conductivereservoir 32. In an exemplary embodiment, the first removable barrier 34may include foil. Prolonged contact between the first conductivereservoir 30 including the therapeutic agent 46 and the first electrode12 may cause degradation of the first electrode 12, the therapeuticagent or both. The first removable barrier 34, which forms the firstbarrier seal, may prevent the first conductive reservoir 30 includingthe therapeutic agent 46 from coming into contact with the firstelectrode 12, thus preventing water transmission. By separating thefirst conductive reservoir 30 from the first electrode 12 with a sealedbarrier (“sealingly separating”) and sealingly separating the secondconductive reservoir 32 from the second electrode 14, the drug deliverysystem 10 maintains efficacy and reliability, thus providing a longershelf-life.

The drug delivery system 10 may also include a housing 38 to house thefirst electrode 12, the second electrode 14, the control circuit 16, thefirst conductive reservoir 30 and the second conductive reservoir 32.The housing 38 has a top housing portion 38 a that is coupleable to abottom housing portion 38 b. The top housing portion 38 a and the bottomhousing portion 38 b are coupled to form a slotted sidewall portion 40 athrough which the first removable barrier 34 extends. Similarly, the tophousing portion 38 a and the bottom housing portion 38 b may form asecond slotted sidewall portion 40 b through which the second removablebarrier 36 extends.

The portion of the first removable barrier 34 that extends outside thehousing 38 provides a user access to the first removable barrier 34without opening the housing. The removable barrier 34 is configured tobe removed while the first electrode 12, the second electrode 14, thecontrol circuit 16, the first conductive reservoir 30 and the secondconductive reservoir 32 remain within the housing. The portion of thefirst removable barrier 34 extending through the slotted sidewallportion 40 a may be in the form of a first tab 34 a. Likewise, a portionof the second removable barrier 36 extending through the second slottedsidewall portion 40 b may be in the form of a second tab 36 a.

A user may remove the first removable bather 34 and the second removablebarrier 36 by pulling on the first tab 34 a and the second tab 36 a,respectively, without accessing the first electrode 12, the secondelectrode 14, the control circuit 16, the first conductive reservoir 30and the second conductive reservoir 32, enabling assembly of aself-contained iontophoretic drug delivery system while components ofthe self-contained iontophoretic drug delivery system remain within thehousing 38.

FIGS. 3 and 4 depict a portion of the exemplary self-containediontophoretic drug delivery system 10 that includes the first electrode12, the second electrode 14 and the control circuit 16. In the sidecross-sectional view depicted in FIG. 3, some thicknesses areexaggerated for illustrative purposes.

The first electrode 12 and the second electrode 14 may be described asan electrode region of the drug delivery system 10. The drug deliverysystem 10 may include at least one battery 18 for providing current tothe control circuit 16, the first electrode 12 and the second electrode14. The control circuit 16 may be electrically connected to at least onebattery 18, the first electrode 12 and the second electrode 14 withcircuitry 20. The circuitry 20, the first electrode 12 and the secondelectrode 14 may be disposed on an electrode support layer 22.

The control circuit 16, the first electrode 12 and the second electrode14 may be supported by a backing layer 24. The electrode support layer22 may be affixed to the backing layer 24.

The drug delivery system 10 may also include a receiving layer 26 thathas a first recess 28 a configured to receive the first conductivereservoir 30 and a second recess 28 b configured to receive the secondconductive reservoir 32.

The current controlled by the control circuit 16 may transdermallydeliver the drug to the user. Iontophoretic transport of the drug isheavily influenced by the current density of the treatment electrode.Thus, the current profile in time may be adjusted to achieve a desiredprofile of drug delivery, i.e. the profile of drug concentration (e.g.,in the plasma) versus time during the total dosing period.

The control circuit 16 may use a configurable microprocessor, aprogrammable microprocessor, a programmable microcontroller, aconfigurable microcontroller or a microprocessor that is bothconfigurable and programmable to set or adjust a desired current profilein time. The total dosing period may be adjusted based on a singlefactor or a combination of factors. Some factors may include, but arenot limited to, the life of the power supply of the system 10, the totalamount of the drug to be delivered, user age, user weight, type of drug,user health, drug delivery protocol, and other like factors.Alternatively, the total dosing period may be set to any time period,e.g. hours, days, or weeks. For example, the total dosing period may beset to a few hours during which high concentrations of a drug arereleased, or the total dosing period may be set to a few weeks duringwhich sustained, low concentrations of a drug are released.

In an exemplary embodiment, the drug delivery system 10 may adjust thedrug delivery profile by adjusting the electrotransport current profile,based on the quantity and/or one or more characteristics of the drug tobe delivered. In an exemplary embodiment, the drug delivery system 10may adjust the drug delivery profile, by adjusting the electrotransportcurrent profile, based on one or more characteristics of the user, e.g.the user's weight, age, health, skin resistance, etc. Theelectrotransport current profile may also be adaptive to yet otherparameters. For example, the system may include one or more sensors formeasuring the concentration of the drug in the user's system (e.g. theuser's blood), and the electrotransport current profile may be adaptiveto the concentration of the drug in the user's system.

In an exemplary embodiment, the microcontroller 150 may be programmedwith a drug delivery profile at the site of manufacture of the drugdelivery system 10. In another exemplary embodiment, the microcontroller150 may be programmed or re-programmed with a delivery profile at thepharmacy subsequent to the manufacture of the drug delivery system 10.In this embodiment, a pharmacist may program or re-program themicrocontroller 150 to achieve a desired drug delivery profile based onthe drug, (e.g. drug concentration, dosage volume, etc) and/or the user(e.g. user size, age, etc). The programming or re-programming of themicrocontroller 150 may adjust one or more aspects of the drug deliveryprofile, e.g. the rate of drug delivery, the concentrations of drugdelivery, etc.

The microcontroller 150 of the drug delivery system 10 may be programmedto drive current of a predetermined profile into the user's skin. Thecurrent profile may not be limited to a particular shape, and mayinclude one or more square waves, sine waves, ramps, arbitrary shapes,or any combination of waveforms, etc.

FIGS. 1-4 depict exemplary embodiments of a drug delivery system (i.e.,a “patch”) having a certain packaging configuration. Other exemplaryembodiments of a drug delivery system as taught herein may havedifferent packaging configurations as taught, for example, in U.S. Pat.No. 6,745,071 to Anderson et al., entitled “Iontophoretic Drug DeliverySystem” or in U.S. patent application Ser. No. 12/181,142 to Anderson etal. published as US Patent Publication No. 2008/0287497 on Nov. 20,2008, entitled “TRANSDERMAL METHODS AND SYSTEMS FOR THE DELIVERY OFANTI-MIGRAINE COMPOUNDS.” U.S. Pat. No. 6,745,071 and US PatentPublication No. 2008/0287497 are incorporated herein by reference intheir entirety.

FIGS. 5-8 depict exemplary current profiles achievable by themicrocontroller 150, where the current is plotted versus time and wherethe current is constant, increasing or decreasing. In FIG. 5, anelectrotransport current is administered for a total dosing period of 4hours. The current is held at 4 mA for the first hour, at 3 mA for thesecond hour, at 2 mA for the third hour, and at 1 mA for the fourthhour. In FIG. 6, the current is held at 4 mA for the first hour, and at2 mA for the next three hours. In FIG. 7, the current is held at 2 mAfor the first and fifth hours, at 0 mA for the second, fourth and sixthhours, and at 3 mA for the third and seventh hours. In FIG. 8, thecurrent is held at 3 mA for the first hour, ramped down to 1 mA duringthe second hour, and held at 1 mA for the third and fourth hours.

The microcontroller 150 may be programmed to achieve a first set ofcurrent levels to be applied during the day and a second set of currentlevels to be applied during the night.

FIG. 9 depicts a block diagram of an exemplary electronic controlcircuit 16 for controlling the drug delivery system 10. The electroniccontrol circuit 16 may include a switch 106 connected to amicrocontroller 150. The microcontroller 150 may also be connected to apower supply 100 and a controllable power supply 200. The controllablepower supply 200 may be connected to a load 300 to drive anelectrotransport current through the load 300. A feedback circuit 250may be connected to the load 300, the controllable power supply 200 andthe microcontroller 150. The electronic control circuit 16 isimplementable on a flexible circuit (e.g. copper on Kapton®), a printedcircuit board or both.

The power supply 100 may provide electrical energy to the circuit. Themicrocontroller 150 may be programmed to control the controllable powersupply 200.

The controllable power supply 200 may increase, decrease or maintain theoutput voltage of the power supply 100 to control load current (I_(L))across load 300. In an exemplary embodiment, the microcontroller 150 mayuse a linear regulator to control the controllable power supply 200. Inanother exemplary embodiment, the microcontroller 150 may use any typeof a switching regulator to control the controllable power supply 200,e.g. pulse width modulation (PWM), pulse frequency modulation (PFM),etc. In an embodiment that employs PWM, the microcontroller 150 mayemploy pulse width modulation, i.e. control a duty cycle and pulsewidth, to control or adjust the load current (k).

The load 300 may include the user's skin, through which a drug isdelivered when the load current is driven across the load 300.

The feedback circuit 250 may allow the microcontroller 150 to detect theload current flowing across the load 300 and the output voltage at theload 300. This allows the microcontroller 150 to monitor and performcurrent correction, i.e. to adjust the load current flowing across theload 300. This also allows the microcontroller 150 to monitor andcontrol the voltage level generated by the controllable power supply200.

In an embodiment that employs a pulse width modulation (PWM)controllable power supply 200, the microcontroller 150 may generatetime-based interrupts and send time-based signals to toggle a switchon/off at the PWM controllable power supply 200. The duty cycle of thePWM controllable power supply 200 is the proportion of time the switchat the PWM is turned on. In order to perform current correction, themicrocontroller 150 may turn the PWM switch off, compare the loadcurrent (I_(L)) to a dynamic value representative of the target loadcurrent value, and adjust the duty cycle of the PWM controllable powersupply 200 based on a result of the comparison. The microcontroller 150may adjust the duty cycle by changing the frequency and/or the durationof the time-based signals which toggle the switch on/off at the PWMcontrollable power supply 200. By adjusting the load current in thismanner, the microcontroller 150 may be able to achieve a load currentprofile that is desirable for delivery of the drug to the user's body.

In some embodiments, the exemplary circuit 900 may be capable of drivingan electrotransport load current (I_(L)) at voltages ranging from 0.4-12V±10%. In some embodiments, the exemplary control circuit 16 may becapable of driving an electrotransport load current (I_(L)) at voltagesranging from 0.4-12 V+10%. In some embodiments, the system resistancesmay be in the range of 200-5,000 Ohms In some embodiments, the systemresistances may be in the range of 100-6,000 Ohms

The exemplary control circuit 16 may be capable of providing a maximumoutput voltage of 12 V to drive an electrotransport load current of 4 mAfor resistances of up to 3,000 Ohms However, in an exemplary embodiment,the control circuit 16 may only provide 10-12 V for up to five minutesduring the first 60 minutes of operation. This five-minute limit on thehigher voltages preserves the battery power.

FIG. 10 depicts a schematic representation of a suitable electroniccircuit 1000 for administering a therapeutic agent or drug. Theelectronic circuit 1000 is one exemplary embodiment of exemplary circuit16.

The system may include a power supply 100 which may include one or morepower sources 102 connected in series or parallel. The number andconnection of power sources, for example, one or more batteries may bedetermined based on the power requirements for the delivery of a drugand the total duration of the circuit's operation. The power supply 100may also include one or more capacitors 104 connected in parallel withthe power source 102.

In one embodiment, the power supply 100 may be integrated with the othercomponents of the drug delivery system 10. In another embodiment, thepower supply 100 may be provided separately from the other components ofthe drug delivery system 10.

The system may include a switch 106 which may be closed to activate thesystem. In an exemplary embodiment, the switch 106 may be a momentaryswitch, e.g. a button or slider, which may be used to activate themicrocontroller 150. In another exemplary embodiment, the switch 106 maybe an on/off switch which may be toggled on/off to activate ordeactivate the microcontroller 150.

The system may also include an on/off indicator, for example, an LED 184connected in series with a resistor 182 if necessary or desirable giventhe operating parameters of the indicator. In an exemplary embodiment,the LED 184 may turn on, turn off or blink to indicate to a user thepresent mode of operation of the system. Moreover, the LED 184 mayindicate, e.g., by turning off, when the dosing period has finished. Inan exemplary embodiment, the LED 184 may be off when the system is in anOff Mode or an Inactive Mode, blink when the system is in a Test Mode,and be on when the system is in a Run Mode. These exemplary modes willbe described in more detail with respect to FIG. 11. In anotherexemplary embodiment, the system may emit an audio tone alone or incombination with the visual indication to indicate that the system is ina certain mode.

The system may also include an external LCD display which may show thepresent electrotransport current, the elapsed time and/or the drugdelivery profile.

The system may include the microcontroller 150 which may implement acontrol loop to achieve a desired drug delivery profile. External nodesmay be provided in the microcontroller for electrical connection to theother components in the circuit. The main function of themicrocontroller 150 is to control the electrotransport load currentdriven across the load 300. In an exemplary embodiment, themicrocontroller 150 may employ a linear regulator to control theelectrotransport load current. In another exemplary embodiment, themicrocontroller 150 may employ any type of a switching regulator, e.g.pulse width modulation (PWM), pulse frequency modulation (PFM), etc. Inan embodiment employing PWM control of the controllable power supply200, the microcontroller 150 may control the electrotransport loadcurrent by either increasing the duty cycle of the PWM controllablepower supply 200 or by decreasing the duty cycle of the PWM controllablepower supply 200.

In one embodiment, the microcontroller may be a PIC12F615, having an8-pin package with flash-based 8-bit complementarymetal-oxide-semiconductor (CMOS) microcontroller manufactured byMicrochip Technology, Inc. A detailed schematic of the PIC12F615microcontroller can be found in the PIC12F609/615/12HV609/615 data sheetpublished by Microchip Technology, Inc. in 2008, incorporated herein byreference. In one embodiment, the microcontroller 150 may bepre-programmed, i.e. may contain a program before being placed in thesystem circuit. In another embodiment, the microcontroller 150 may beprogrammed after its placement in the system circuit.

In an exemplary embodiment, the microcontroller 150 may be programmedonly once. In another exemplary embodiment, the microcontroller 150 maybe programmed a first time with a first current profile. Themicrocontroller 150 may be re-programmed, i.e. programmed a second time,with a second current profile. This re-programming of themicrocontroller 150 allows alteration or correction of a currentprofile, and also allows the same system to be reused for differentusers and/or different drugs.

The programming of the microcontroller 150 will now be described indetail. In order to program the microcontroller 150, a programmer maygenerate a program in a suitable format, e.g. in a HEX file, to specifyhow the non-volatile memory bits of the microcontroller 150 are to beset. The programmer may then use a programming interface 170 to storethe program in the microcontroller 150. The programming interface 170may be connected to an I/O port of a PC (not pictured) on one side andto the microcontroller 150 on the other side. In an exemplaryembodiment, the programming interface 170 is an in-circuit programminginterface which may connect to the microcontroller 150 while themicrocontroller is connected to the system circuit. In this embodiment,program data may be transferred to the microcontroller 150 using atwo-wire synchronous serial scheme with a clock controlled by theprogramming interface 170.

The ground (GND) node 180 of the programming interface 170 may beconnected to the negative power input (VSS) at node 160 of themicrocontroller 150. The positive power input (VDD) node 172 of theprogramming interface 170 may be connected to the positive power input(VDD) at node 152 of the microcontroller 150. The programming voltage(MCRL) node 178 of the programming interface 170 may be connected to theprogramming mode voltage at node 158 of the microcontroller 150. To putthe microcontroller 150 into the programming mode, this MCRL line mustbe in a specified range above the VDD line. The programming clock (PGC)node 176 of the programming interface 170 is the clock line of theserial data interface and may be connected to node 164 of themicrocontroller 150. The voltage at the PGC node 176 swings from GND toVDD, and data is transferred on the falling edge. The programming data(PGD) node 174 of the programming interface 170 is the serial data lineand may be connected to node 162 of the microcontroller 150. The voltageat the PGD node 174 swings from GND to VDD.

The connections of the external nodes of the microcontroller 150 willnow be listed. Node 152 is the positive power input (VDD) to themicrocontroller 150, and may be connected to the power supply 100. Node154 is an output node coupled to a switch of the controllable powersupply 200 to allow the microcontroller 150 to control the operation ofthe controllable power supply 200. The node 154 may be connected to thegate of a switch 202. In an exemplary embodiment, the switch 202 may bea p-channel metal-oxide-semiconductor field-effect transistor (MOSFET)202. Node 156 may be connected to the positive terminal of the senseresistor 256. Node 158 may be connected to the MCRL node 178 of theprogramming interface 170. Node 160 is the negative power input to themicrocontroller 150 and may be connected to the negative terminal of thesense resistor 256 to allow the microcontroller 150 to monitor the loadcurrent (I_(L)) across the load 300. Node 162 may be connected to thePGD node 174 of the programming interface 170. Node 164 may be connectedto the external switch 106 of the system. Node 166 may be connected tothe voltage divider created by resistors 252 and 254 to allow themicrocontroller 150 to monitor the voltage generated by the controllablepower supply 200.

In an exemplary embodiment (not depicted in FIG. 10), the controllablepower supply 200 may be configured as a buck-boost converter whichallows the output voltage at the load 300 to be higher or lower than thepower source 102 voltage. The “boost” stage refers to output voltagesabove the power source 102 voltages, and the “buck” stage refers tooutput voltages below the power source 102 voltage.

In another exemplary embodiment (depicted in FIG. 10 and describedfurther below), the controllable power supply 200 may include a standardinverse single-ended primary inductor converter (SEPIC). In thisembodiment, the controllable power supply 200 may include a resistor 204which has a positive terminal connected to the positive terminal of thepower source 102 and a negative terminal connected to the node 154 ofthe microcontroller 150. The controllable power supply 200 may alsoinclude a switch 202 which has a gate connected to the node 154 of themicrocontroller 150, a source connected to the positive terminal of thepower source 102, and a drain connected to a positive terminal of thefirst inductor 208 and a positive terminal of the first capacitor 206.The resistor 204 and the switch 202 in the controllable power supply 200may work in conjunction with the microcontroller 150 to act like aswitch and gate the power supply voltage into a first inductor 208.

The controllable power supply 200 may include the first inductor 208which has a first terminal connected to the drain of the switch 202 anda first terminal of the first capacitor 206. The first inductor 208 mayhave a second terminal connected to the negative terminal of the powersource 102. The controllable power supply 200 may include a firstcapacitor 206 which has a first terminal connected to the first terminalof the first inductor 208 and to the drain of the switch 202. The firstcapacitor 206 may have a second terminal connected to a second terminalof a second inductor 212 and to a first terminal of a Schottky diode210.

The controllable power supply 200 may include the Schottky diode 210which has a first terminal connected to the first terminal of the firstcapacitor 206 and the second terminal of the second inductor 212. TheSchottky diode 210 has a second terminal connected to the negativeterminal of the power source 102. The controllable power supply 200 mayinclude a second inductor 212 which has a first terminal connected tothe second terminal of the first capacitor 206 and to the first terminalof the Schottky diode 210. The second inductor 212 has a second terminalconnected to a voltage divider and to a first terminal of a secondcapacitor 214. The controllable powers supply 200 may include the secondcapacitor 214 which has a first terminal connected to the voltagedivider and the second terminal of the second inductor 212.

The second capacitor 214 has a second terminal connected to the negativeterminal of the power source 102.

The load 300 may be coupled between the first electrode 302 and thesecond electrode 304 which may be applied to the user's skin.

The feedback circuit 250 may include a voltage divider formed by a firstresistor 252 and a second resistor 254. The first resistor 252 may havea first terminal connected to the second terminal of the second inductor212 and to the first terminal of the second capacitor 214. The firstresistor 252 may have a second terminal connected to the first terminalof the second resistor 254. The second resistor 254 may have a secondterminal connected to the negative terminal of the power source 102. Thevoltage divider allows the microcontroller 150 to monitor and controlthe voltage generated by the controllable power supply 200. The feedbackcircuit 250 may also include a sense resistor 256 which may be used todetect the electrotransport current flowing between the electrodes 302and 304.

Operation of the exemplary circuit 1000 will now be described inrelation to FIG. 11. FIG. 11 depicts a flow diagram of an exemplarycontrol loop implemented by the exemplary electronic circuit depicted inFIG. 10.

The exemplary circuit 1000 is described with reference to a pulse widthmodulation (PWM) power supply 200, i.e. a controllable power supply 200controlled by the PWM. Nonetheless, the present invention is not meantto be limited to this particular embodiment of a controllable powersupply 200. Exemplary embodiments may also employ other types ofcontrollable power supplies 200, e.g. a linear regulator-controlledpower supply, any type of a switching regulator-controlled power supply,etc.

The system may be kept in an Off Mode from the time the device isassembled until a user activates the external switch 106 to turn on thesystem. In the Off Mode, the microcontroller 150 may perform someminimal operations, e.g. detect activation of the system by a user usingthe external switch 106. While in the Off Mode, the system may provide avisual or auditory indication that the system is in the Off Mode and hasnot yet been activated. In an exemplary embodiment, the LED 184 may beoff during the Off Mode.

In step 504, the user may close the external switch 106 to turn on thesystem. To prevent accidental activation of the system, in an exemplaryembodiment, the user may need to press on the switch for a minimumperiod of time, e.g. 1 second, to turn on the system.

Upon closing of the external switch 106, the system may enter a TestMode before beginning a dosing mode for dosing of the drug. An exemplaryTest Mode is described with reference to steps 506 and 508. When in theTest Mode, the system may provide a visual or auditory indication thatthe system is in the Test Mode. In an exemplary embodiment, the LED 184may blink during the Test Mode.

In step 506, before beginning dosing of the drug, the microcontroller150 may determine if the power supply 100 has sufficient storedelectrical energy to complete the full dosage protocol of the drug. Insome circumstances, the stored energy of the power supply 100 may becomedepleted even before use, e.g. if the power supply is defective, rundown and/or was accidentally turned on numerous times during handling.It may be risky to initiate drug delivery with such a depleted powersupply, because the user may receive a less than intended dosage if thepower supply runs out before the end of the full dosing period.

To prevent the user from operating the system with a depleted powersupply, in step 506, the microcontroller 150 may detect the voltage ofthe power supply 100 at node 152, and determine if this voltage is abovea minimum threshold voltage. This minimum threshold voltage may be thepower supply voltage required to deliver the total dosage of the drug.If the power supply voltage is determined to be lower than the minimumthreshold voltage, then the system may not be activated and may enter anInactive Mode. The output current of the system during the Inactive Modemay be less than 10 μA, which does not deliver any significant amount ofthe drug. The system may provide a visual or auditory indication thatthe system is in the Inactive Mode. In an exemplary embodiment, the LED184 may be off during the Inactive Mode.

In one embodiment, the power supply 100 may be provided separately fromthe system circuitry. In this case, the user may replace the old powersupply 100 with a new power supply, and re-activate the system.

In step 506, if the power supply voltage is determined to be equal to orhigher than the minimum threshold voltage, then the control loop mayadvance to step 508.

In some circumstances, the user may mistakenly press the switch 106before applying the drug delivery system to his/her body. To preventdosing from beginning in such circumstances, the microcontroller 150 maystart dosing of the drug only after the electrotransport current reachesa minimum level. In step 508, the microcontroller 150 may determine ifthe electrotransport current has reached a minimum level, e.g. 1 mA, andmay begin dosing according to the programmed current profile only afterthis minimum level is reached. However, if the electrotransport currentdoes not reach the minimum level within a certain time of activation ofthe switch 106, e.g. 5 minutes during which time the LED 184 flashes,then the system circuit may not be activated and the system may enterthe Inactive Mode. The system circuit may later be restarted.

In step 510, the system may enter a Run Mode and may begin dosing of thedrug according to the electrotransport current profile programmed in themicrocontroller 150. The system may provide a visual or auditoryindication that the system is in the Run Mode. In an exemplaryembodiment, the LED 184 may be on to indicate that the system is in theRun Mode. The system may monitor the time elapsed since entering the RunMode.

When an electrotransport current is first applied to the user's skin,the skin resistance tends to be high and gradually decreases as thecurrent continues to be applied. In step 512, immediately after enteringthe Run Mode, the microcontroller 150 may first output a predeterminedPWM waveform for 10 msec before any adjustments are made to the waveformto account for skin resistance. In an exemplary embodiment, themicrocontroller 150 may be programmed to measure the user's skinresistance, and determine the time period required in step 512 duringwhich no adjustments are made to the PWM waveform to account for skinresistance.

In step 514, the PWM power supply 200 may operate in its “on” stage.During steps 516-528, the PWM power supply 200 may operate in its “off”stage. The operation of the PWM power supply 200 will now be describedin more detail.

The switch 202 and the resistor 204 may work in conjunction with themicrocontroller 150 to gate the power supply voltage into the inductor208. The gating of the power supply voltage into the inductor 208 maycontrol the amount of load current through the load 300. Themicrocontroller 150 may control the electrotransport current byadjusting the duty cycle of the PWM power supply 200, i.e. by adjustingthe proportion of time that the switch 202 is “on.”

During the “on” stage of the PWM power supply 200, node 154 of themicrocontroller 150 may apply a voltage at the gate of the switch 202 toclose the switch 202. Closing the switch 202 may direct the power source102 voltage into the inductor 208, which also adds to the voltage acrossthe capacitor 206.

During the “off” stage of the PWM power supply 200, node 154 of themicrocontroller 150 may turn off the voltage at the gate of the switch202 to open the switch 202. When the switch 202 opens, electrical energystored in the magnetic field around the inductor 208 may keep currentflowing through the inductor 208 by forcing the Schottky diode 210 toact as a “free wheeling diode.” This may continue to drive currentthrough the inductor 212. The current through the inductor 212 maydivide between supplying the voltage divider, charging the capacitor214, and supplying the electrodes 302 and 304.

The operating frequency of the system may vary depending on the loadresistance. In an exemplary embodiment, the system may operate at about156 kHz for high load resistances and at about 78 kHz for low loadresistances. This variation in operating frequencies overcomes anyhardware-imposed limitations on the minimum “on” time of the PWM powersupply 200.

During normal operation, the system may monitor the electrotransportcurrent through the electrodes, and compares the detectedelectrotransport current to a dynamic value representative of the targetcurrent. Based on this comparison, the system may increase or decreasethe electrotransport current by controlling the duty cycle of the PWMpower supply 200 described above. The duty cycle of the PWM power supply200 described above is the proportion of time the switch 202 is in the“on” state. In exemplary embodiments, the microcontroller 150 may adjustthe duty cycle by changing the frequency and/or the duration of thetime-based signals which turn on/off the switch 202.

In step 516, a timer in the microcontroller 150 may generate one or moreinterrupts at intervals, e.g. at 10 msec intervals. The interrupts maybe generated by a timer function in the microcontroller 150. Themicrocontroller 150 may have a clock oscillator. In an exemplaryembodiment, the clock oscillator may run at 8 MHz and may be specifiedto an accuracy of +2%. The timer function may count the number ofmicrocontroller clock cycles, and compare the timer value with a fixednumber representing the desired time. In an exemplary embodiment, thetimer may run on the main clock, e.g. at 8 MHz, and may generateinterrupts at 10 millisecond intervals.

The second capacitor 214 may maintain the output voltage and currentflow, and thereby valid readings in the circuit.

In step 518, upon the generation of each interrupt, the microcontroller150 may turn off the switch 202. During the “off” stage of the switch202, the microcontroller 150 may determine the output voltage appliedacross the load 300, determine the electrotransport current flowingacross the load 300, and a digital representation of an internal bandgapvoltage contained in the microcontroller 150. Using these values, themicrocontroller 150 may determine if the duty cycle of the PWM powersupply 200 needs to be adjusted to set the electrotransport current to adesired level.

In step 520, during the “off” stage of the switch 202, themicrocontroller may determine a digital representation of theelectrotransport current flowing across the load 300. Theelectrotransport current may be determined by the voltage drop acrossthe sense resistor 256 which is connected in series with the electrodes302 and 304. Nodes 156 and 160 of the microcontroller may be connectedto the positive and negative terminals, respectively, of the senseresistor 256 to detect the voltage across the sense resistor. Ananalog-to-digital converter (ADC) in the microcontroller 150 may detectthe voltage drop across the sense resistor 256, and determine a digitalrepresentation of the electrotransport current by dividing this voltageby the resistance of the sense resistor 256.

The microcontroller may also determine a digital representation of theoutput voltage applied across the load 300. The output voltage may bedetermined using the voltage divider composed of resistors 252 and 254.The voltage divider may reduce the detected voltage to a range capableof being processed by the ADC in the microcontroller 150. Node 166 ofthe microcontroller may be connected between the resistors 252 and 254of the voltage divider. The ADC in the microcontroller 150 may read thevoltage applied across the resistor 254, and determine a digitalrepresentation of the output voltage applied across the electrodes basedon this voltage.

In an exemplary embodiment, the ADC in the microcontroller 150 may be a10-bit successive approximation type ADC (1024 counts full scale). Thefull scale of the ADC is the power source 102 voltage.

In step 522, during the “off” stage of the switch 202, themicrocontroller 150 may determine the dynamic value representative ofthe target current and the dynamic value representative of the targetvoltage. In an exemplary embodiment, the electrotransport current andoutput voltage values determined by the microcontroller 150 may first bemultiplied by a calibration value which corrects for variability in thebandgap reference.

As described above, the microcontroller 150 may use an ADC to convertmeasured voltages and currents to their respective digitalrepresentations. The ADC may use a reference voltage for conversionpurposes which may be supplied by the power supply 100.

Operation of the system circuit may reduce the voltage of the powersupply 100 which, in turn, may reduce the reference voltage of the ADC.The microcontroller 150 may account for this gradual reduction in theADC reference voltage by recalculating the dynamic values and voltagevalues upon the generation of each interrupt. As the reference voltagedecreases, the microcontroller 150 may also perform a reverse correctionby expanding its voltage scale to increase the granularity of voltagereadings.

In an exemplary embodiment, the dynamic values representative of thetarget current and the target voltage may then be determined based onthe following equations. The electrotransport current (i) used in thefollowing equations may be read from the desired electrotransportcurrent profile programmed in the microcontroller 150. The voltage (v)used in the following equations may be the maximum voltage allowed inthe system.

Dynamic value representative of a target electrotransport current of imA=((Bandgap Voltage×i mA×resistance of the sense resistor 256)/1.20 Vreference)×256 bit shift×100.6 nominal reference value

Dynamic value representative of a target output voltage of v V=(BandgapVoltage×v V× 1/16 resistor divider)/1.20 V reference)×256 bitshift×100.6 nominal reference value

The microcontroller 150 may account for the reduction in the ADCreference voltage by recalculation of the dynamic values representativeof the target current and the target voltage upon the generation of eachinterrupt. Calculation of the dynamic value representative of the targetcurrent is based on the target current value, the sense resistor value,the measured bandgap voltage value, a fixed voltage value and aconstant. In turn, the digital representation of the current through thesense resistor is compared to the dynamic value representative of thetarget current to determine if the current through the sense resistormatches the target current value.

In step 524, during the “off” stage of the switch 202, themicrocontroller 150 may digitally compare the output voltage with thedynamic value representative of the target voltage, and theelectrotransport current with the dynamic value representative of thetarget current. When driven, the second capacitor 214 has an associatedripple current. During the “off” stage of the switch 202, this ripplecurrent is eliminated.

In step 526, during the “off” stage of the switch 202, if the outputvoltage is greater than the dynamic value representative of the targetvoltage, then the microcontroller 150 may decrease the duty cycle of thePWM power supply 200 by one step. This step allows the microcontrollerto maintain the output voltage below a certain maximum levelirrespective of changes in the resistance of the user's body to avoidburning the user's skin. No current correction is performed in step 526.

In step 528, during the “off” stage of the switch 202, if the outputvoltage is equal to or less than the dynamic value representative to thetarget voltage, then the microcontroller 150 may perform currentcorrection in step 530. In step 530, during the “off” stage of theswitch 202, the microcontroller 150 may perform current correction basedon three conditions outlined in steps 532-536.

If the electrotransport current is greater than the dynamic valuerepresentative of the target current, then the microcontroller 150 maydecrease the duty cycle of the PWM power supply 200 by one step in step532. If the electrotransport current is equal to the dynamic valuerepresentative to the target current, then the microcontroller 150 maynot alter the duty cycle of the PWM power supply 200 in step 534. If theelectrotransport current is less than the dynamic value representativeof the target current, then the microcontroller 150 may increase theduty cycle of the PWM power supply 200 by one step in step 536.

In addition to the control loop depicted in FIG. 11, the system maymonitor the electrotransport current and the output voltage at regularintervals, e.g. 100 Hz. The system may also perform one or more safetytests at regular intervals, e.g. once per second.

If the voltage of the power supply 100 falls below a certain limitduring operation, there is a risk that the microcontroller 150 may stopworking correctly or shut down. In an exemplary embodiment, themicrocontroller 150 may detect this risk by monitoring if the powersupply voltage has fallen below a minimum threshold voltage. The minimumthreshold voltage may be a voltage below which there is a risk that themicrocontroller 150 may stop working correctly or shut down. Thisminimum threshold voltage may be read off from the datasheet of themicrocontroller 150 and adjusted based on the voltage tolerance of themicrocontroller. If the power supply voltage is below the minimumthreshold voltage, the microcontroller 150 may stop its operation of thesystem and the system may enter the Inactive Mode. If the power supplyvoltage is equal to or above the minimum threshold voltage, the systemmay continue to operate and may remain in the Run Mode.

In an exemplary embodiment, the system may monitor if theelectrotransport current is too high (e.g. exceeds 6 mA) for a specifiedtime (e.g. a period exceeding 60 consecutive seconds). In an exemplaryembodiment, the system may monitor if the output voltage is too high(e.g. 14 V) for a specified time (e.g. 60 consecutive seconds). In anexemplary embodiment, the system may monitor if the electrotransportcurrent is too low (e.g. remains below 0.2-0.4 mA) for a specified time(e.g. a period exceeding 1 hour). In one embodiment, this specifiedperiod (e.g. 1 hour) may be cumulative and may include discontinuousperiods of time. In another embodiment, this specified period may benon-cumulative and may only include one continuous period of time. Ineach case, if the condition is satisfied, the microcontroller 150 maystop operation of the system and the system may enter the Inactive Mode.However, if the condition is not satisfied, the system may continue tooperation and may remain in the Run Mode.

In an exemplary embodiment, if the system enters the Inactive Mode dueto any of the aforementioned checks, an indicator may be activated toalert the user that the system circuit is in the Inactive Mode. In anexemplary embodiment, this indication may be provided by turning off theLED 184 or emitting an audio tone.

The system may be deactivated at the end of the total dosing period, asdetermined from the programming of the microcontroller 150. At the endof a successful dosing period, the system may provide a visual orauditory indication that dosing has ended. In an exemplary embodiment,this indication may be provided by turning off the LED 184 or emittingan audio tone.

In an exemplary embodiment, the device is disposable after a single use.In this embodiment, the microcontroller 150 may be programmed to preventreuse at the end of the total dosing period. At the end of the totaldosing period, the microcontroller 150 may be left on to slowly drainthe power supply 100. This would eliminate any risk of the devicesubsequently turning back on. Alternatively, at the end of the totaldosing period, the microcontroller 150 may automatically turn on ifturned off at the end of the total dosing period to slowly drain thepower supply 100

In another exemplary embodiment, the device may be configured formultiple uses. In this embodiment, the microcontroller 150 may beprogrammed to allow reuse at the end of the dosing period, and themicrocontroller 150 will not enter a mode intended to drain the powersupply 100 to prevent reuse.

The control loop described above is an incremental control. Suchincremental control is appropriate for the drug delivery system becausechanges on the load presented by the patch will be relatively slow.Chemical changes are likely to take seconds to minutes to causesignificant current changes. Even changes due to movement of the patchwill occur over hundreds of milliseconds.

In another aspect, the invention provides methods of delivering atherapeutic agent, e.g., sumatriptan succinate, to a user employing anyof the drug delivery systems described herein.

In still other aspects, the present invention is directed to methods fortreating a user. The method generally includes transdermallyadministering to the user an effective amount of a drug, wherein thedrug is administered using any one of the drug delivery systems usedherein.

The drug delivery systems may be applied to any appropriate surface ofthe user. In some embodiments, the device is applied to the upper arm,leg (e.g., thigh), or back (e.g., upper back). In some embodiments thedrug delivery system is worn for a prescribed period of time, e.g.,about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours. For example, in oneembodiment, the drug delivery system includes sumatriptan succinate andis applied to the upper arm or back for about 4 or 5 hours. In anotherembodiment, the drug delivery system including sumatriptan succinate isapplied to the upper arm or back for about 6 hours.

Examples of a therapeutic drug or agent include, but are not limited toan analgesic, anesthetic, anti-arthritis drug, anti-inflammatory drug,anti-migraine drug, cardiovascularly active drug, smoke cessation drug,hormone, non-steroidal anti-inflammatory agent, anti-hypertensive agent,analgesic agent, anti-depressant, antibiotic, anti-cancer agent, localanesthetic, antiemetic, anti-infectant, contraceptive, anti-diabeticagent, steroid, anti-allergy agent, agents for smoking cessation, oranti-obesity agent. Examples of therapeutic drugs or agents include, butare not limited to, nicotine, androgen, estrogen, testosterone,estradiol, nitroglycerin, clonidine, dexamethasone, wintergreen oil,tetracaine, lidocaine, fentanyl, sufentanil, alfentanil, progestrone,insulin, Vitamin A, Vitamin C, Vitamin E, prilocaine, bupivacaine,scopolamine, dihydroergotamine, and pharmaceutically acceptable saltsthereof. In a further embodiment, the therapeutic agent is a triptancompound, e.g., sumatriptan, almotriptan, zolmitriptan, rizatriptan,naratriptan, or a combination thereof.

The triptan compound may have a responsive state which is at least onestate selected from a group consisting of migraines, familiar hemiplagicmigraines (with and without aura), chronic paroxysmal headaches, clusterheadaches, migraine headaches, basilar migraines, and atypical headachesaccompanied by autonomic symptoms.

In an exemplary embodiment, the therapeutic agent is a triptan compoundand the state which is treated is a triptan compound responsive state,e.g., states which can be treated by the administration of a triptancompound. Triptan compound responsive states include almotriptanresponsive states, zolmitriptan responsive states, rizatriptanresponsive states, sumatriptan responsive states, and naratriptanresponsive states. The term also includes migraines, familiar hemiplegicmigraines (with and without aura), chronic paroxysmal headaches, clusterheadaches, migraine headaches, basilar migraines, and atypical headachesaccompanied by autonomic symptoms.

The term “treated,” “treating” or “treatment” includes therapeuticand/or prophylactic treatment. The treatment includes the diminishment,alleviation of at least one symptom, or complete eradication of a stateor condition.

As taught herein, an exemplary electrode continuity test apparatus maybe used for the testing and verification of the function and operationof the electrical connections of the drug delivery system 10 (i.e.,iontophoretic drug delivery systems as taught herein). Such exemplarytest and verification electrode continuity tester may include anelectrode patch continuity test apparatus that is adapted for use in thetesting and verification of the electrode connections of the drugdelivery system 10.

In certain non-limiting examples, one exemplary electrode continuitytest apparatus includes a flat base panel onto which two copper stripsare adhered. The copper strips are connected to a switch located insidean enclosure connected to the base panel. A 1 kΩ resistor is connectedin-line with one of the copper strips.

The exemplary electrode continuity test apparatus further includes a topplate having a hole cut in it to permit access to the top of the drugdelivery system 10. The top plate is affixed to the base panel. The topplate may be affixed to the base panel by any means known in the art foraffixing two layers such that they may be securely layered one on top ofthe other. For example, the top plate may be affixed to the base panelby a hinge. In certain embodiments, the top plate includes two rubber orfoam rings or solid circles that provide pressure to the iontophoreticsystem when it is placed between the top plate and the base panel andthe top plate is closed on top of the base panel. This pressure providescontact between the printed electrodes of the drug delivery system 10and the copper strips of the base panel. Pressure is maintained by meansof a fastening tool which secures the top plate onto the base panel toform a layered structure. For example, the fastening means may be alatch which is attached to the top plate and having a means such thatthe top plate may be secured to the base panel.

FIG. 12 is a block flow diagram depicting an exemplary method for thetesting and verification of the electrical connections of the drugdelivery system 10. Exemplary methods include the step 801 of placingthe drug delivery system 10 on the base panel. In step 802, the printedelectrodes are placed in contact with the copper strips of the electrodecontinuity test apparatus. In step 803, the top plate is closed on topof the drug delivery system 10. In step 804, the top plate is secured tothe base panel by the fastening tool. For example, the drug deliverysystem 10 may be placed on the base panel such that the electrodes ofthe drug delivery system 10 are placed in contact with the copper stripsof the base panel and the top plate is fasted to the base panel forminga layered device wherein the drug delivery system 10 is sandwichedbetween the base panel and the top plate. The top plate includes a holetherein, whereby access to the control circuit 16 of the drug deliverysystem 10, as depicted in FIG. 2, is provided. If needed, a power supplyis connected to the drug delivery system 10. In step 805, the switch 106is depressed through the hole in the top plate for about 2-8 seconds.The drug delivery system 10 includes a LED 184 as depicted in FIG. 10.In step 806, the switch 106 is depressed for 2-8 seconds, whereby theLED 184 should blink, indicating that the drug delivery system 10 is intest mode. In step 807, the switch 106 is then pressed and the LED 184changes to a fully illuminated state. This indicates that the connectionbetween the power supply and the electrode(s) of the drug deliverysystem 10 are functional.

The electrode continuity test apparatus taught herein provides a rapidfunctional and operational assessment of the drug delivery system 10.The test apparatus and methods evaluate whether the connections betweenthe electrode and the circuit board assembly of the drug delivery system10 are compromised, for example damaged due to shipping and handling andprocessing of the drug delivery system 10.

Exemplary methods may also include methods for testing and measuring thecapacity of the electrode of the drug delivery system 10, as taughtherein, to deliver a targeted quantity of the drug.

As used herein, the term “capacity” refers to the measurement of theability of the drug delivery system to delivery a targeted quantity ofdrug (i.e., over a targeted time interval). Testing and calculation ofthe capacity ensures that there is enough of the chosen metals todeliver the targeted amount of drug to a subject.

For example, the drug delivery system 10 may include a silver chloride(AgCl) cathode and a zinc (Zn) anode that is used to deliver across theskin of a user an active agent such as, for example, sumatriptan whichis a positively charged drug. At the same time, negatively charged ionsin the body move away from the silver chloride (AgCl) cathode towardsthe positive anode. The conductive metal for the electrodes provides theions that participate in the electrochemical reactions integral to theiontophoretic process.

The quantity and availability of the ions present on the electrode aredirectly proportional to the ability of the iontophoretic reaction tocontinue. The electrochemical capacity must be sufficient to support theiontophoretic function of the drug delivery system 10 over the intendedtime period of use. The target amount of capacity required is determinedby factoring into account the total amount of current being provided tothe drug delivery system 10 and the total amount of time the drugdelivery system 10 is intended to be worn. The electrochemical capacityof an electrochemical cell is limited by the capacity of the anode andcathode electrodes, while operating within their primaryelectrochemistry. Capacity in this sense is defined as the integralproduct of applied current and time. Thus the capacity of the drugdelivery system 10 cannot exceed that of either the anode or cathodehalf-cells.

An electrochemical transition between a primary electrochemistry and asecondary electrochemistry can be generalized as a period of relativelyconstant voltage, followed by an inflection region of high curvature, arelatively steep voltage-time slope, another inflection region with theopposite curvature to the first inflection, and then finally a voltageplateau representing the secondary electrochemistry.

For purposes of the various embodiments of the drug delivery system 10,the capacity is measured at a consistent point in one of the twoinflection zones. In the case of the cathode, the primary Ag/Ag-Clreduction electrochemistry is followed by a secondary reductionelectrochemistry of water-splitting, which can cause skin irritation dueto creation of a highly basic local environment. For this reason, thecathode transition is defined to occur at the first inflection point.For the anode, the primary zinc oxidation electrochemistry is succeededby a more benign Ag oxidation electrochemistry. Therefore, the anodeendpoint is defined as occurring at the second inflection point.

The method of capacity test, provided herein is achieved by monitoring acontrolled current discharge of the Zn anode and the Ag/AgCl cathodepair separated by a dissimilar pair of gel pads identical to those usedin the end application. The pad facing the anode consists of polyaminegel containing, for example, 4% by weight of sumatriptan succinateimbibed into a non-woven rayon pad. The present embodiments areexemplary and the drug delivery system 10 contemplates further agentsbeyond sumatriptan. The cathode-facing pad consists of a gel containing,for example, 0.9% NaCl by weight imbibed into a non-woven rayon pad. Thecurrent used during discharge is specified by an exemplary currentprofile of 4 mA for 1 hour followed by 2 mA for 3 hours with a minimumtest duration of about 5 hours, more preferably about 5.5 hours. Forexample, 1 hour at 4 mA and 4.5 hours at 2 mA. The anode and cathodepotentials are monitored during the test with respect to two Ag/AgClreference electrodes. Electrode capacity in this test is defined by theintegrated current-time product measured at the point when a givenelectrode deviates from its characteristic reaction, as indicated by themeasured electrode potential.

FIG. 13 is a block flow diagram depicting exemplary steps of a methodfor measuring the capacity. In step 901, a performance evaluation isdone on the test assembly by measuring and recording the voltage of thetest assembly. For example, test clips are attached to a referenceresistor connector and software is provided whereby the voltage acrossthe test assembly is measured and recorded. Continuing with step 901,the voltage is compared to a base or nominal voltage value over specifictime intervals. For example, over a time window of 0-12 seconds thenominal voltage is 0.02 v for the anode and −0.02 v for the cathode. Apassing measurement for this time interval falls within +/−0.01 v. Forthe time interval of 15-27 seconds the nominal voltage for the anode is0.22 v and −0.22 v for the cathode. A passing measurement for this timeinterval falls within +/−0.02 v. For the time interval of 30-42 secondsthe nominal anode voltage is 0.44 v while the nominal cathode voltage is−0.44 v. A passing measurement for this time interval falls within therange of +/−0.02 v. For the time interval of 45-57 seconds, the nominalvoltage for anode and cathode are 0.88 v and −0.88 v, respectively. Apassing measurement for this time interval falls within +/−0.04 v ofthose values. For the time interval of 60-72 seconds the nominal anodeand cathode voltage are 0.02 v and −0.02 v, respectively. A passingmeasurement for this time interval falls within +/−0.01 v. In step 902,voltage measurements that fall outside the passing measurements indicatethat the test assembly is defective and may be subjected to a retest.Other exemplary embodiments of the drug delivery system 10 contemplatealternative nominal values and passing ranges.

In step 903, a package having both an anode and a cathode is cut suchthat the anode is separated from the cathode. In step 904, the cathodeand the anode are respectively labeled to preserve their identity. Instep 905, the anode is placed on a surface, for example, a table. Theanode includes an electrode tail and opposing surfaces with one surfacehaving a conductive ink. The anode is placed on the surface such thatthe conductive ink is facing up and the electrode tail is at the 12o′clock position. In step 906, with the ink side up, a square printedend of a reference electrode is folded over about ¼ of an inch from theend. In step 907, the reference electrode is placed approximately ¼ ofan inch to the side of the labeled anode. The folded end of thereference electrode is projected past the end of the backing in the samedirection as the tail of the electrode. In step 908, the referenceelectrode is secured to a polyester material with a securing mechanism,for example, a piece of tape such that the tape does not contact theelectrode ink. In step 909, steps 905 through 908 are repeated for thelabeled cathode portion previously separated from the anode.

In step 910, a HPC salt package is opened and the HPC salt pad is usedto smear the residue on to the cathode such that substantially all ofthe surface, preferably 100%, of the cathode electrode circle and thereference electrode are covered. In step 911, using forceps or othertype of gripping means, the HPC pad is removed and placed on thecathode. In step 912, the edge of the pad is contacted and rolled ontothe cathode, covering the cathode and reference electrode. In step 913,a wet preparation start time is recorded.

In step 914, a polyamine package containing a polyamine pad is openedand using forceps or other type of gripping means. In step 915 thepolyamine pad is applied to the HPC pad as described for the HPC pad sothat the edges of both the HPC and polyamine pads are aligned. Thepolyamine residue from the polyamine package is smeared onto the anodecovering substantially all the surface of the anode electrode circle.Preferably 100% of the surface is covered. In step 916, the anode isplaced on top of the polyamine pad using a rolling method. Theconductive ink die is faced down and is in contact with the polyaminepad. The tails of the anode and anode reference electrodes should beoffset from the cathode electrode pair by approximately 1 inch.

In step 917, the assembled electrode pair is placed on a mounting board.In step 918, the electrode pair is secured to the mounting board,preferably by tape or other suitable adhesive means. In step 919, thesurface of the assembled electrode pair is gently smoothed away toremove any trapped air bubbles. In step 920, the wires from a driverboard are attached by clipping a first wire to the anode referenceelectrode; clipping a second wire to the anode; clipping a third labeledwire to the cathode; and clipping a fourth labeled wire to the cathodereference electrode. In step 921, the voltages for the anode and cathodeare verified. For example, valid voltages may fall within the range of−0.9 to −1.2 volts for the anode and 0 to −0.1 volts for the cathode. Instep 922, the voltages are recorded. In step 923, a polycarbonate blockis placed on top of the electrode assembly with one of the cornersbetween the anode and cathode connections. That corner is secured to themounting board. In step 924, the entire assembly is then placed into are-sealable plastic bag. In step 925, the capacity is measured. Forexample, capacity software is executed for the measurement andrecordation of voltage readings at the cathode and anode. In step 926,the capacity of the electrodes is calculated.

In certain other embodiments of the apparatus and the methods of thepresent invention, the electrotransport current follows a predeterminedcurrent-time profile.

In certain other embodiments of the methods disclosed herein, an outputvoltage applied across the animal body surface is maintained below amaximum value irrespective of changes in a resistance of the animal bodysurface to avoid burning the animal body surface. In certain otherembodiments the methods further comprises the steps of detecting ifthere is a minimum level of energy in a battery of the device anddriving the electrotransport current through the animal body surfaceonly if the battery has the minimum level of energy.

In other embodiments, the method further comprises the steps of shuttingdown the device upon detecting a potential safety issue and providing anindication that the device has been shut down.

In some embodiments, the indication is the turning off of an LED lightin the device. In certain other embodiments the indication is theplaying of an audio tone by the device.

Certain other embodiments of the methods disclosed herein furthercomprises the steps of immediately after turning on the drug deliverydevice, applying an output voltage across the animal body surface for apredefined time duration without controlling the duty cycle of the PWMpower supply.

In other embodiments, the methods comprise controlling theelectrotransport current in a predetermined profile, wherein thepredetermined profile of the electrotransport current includes a firstfixed current value for a first predetermined time duration and a rampof increasing or decreasing current values for a second predeterminedtime duration.

In other embodiments, the methods further include controlling theelectrotransport current in a predetermined profile, wherein thepredetermined profile comprises a first fixed current value for a firstpredetermined time duration and a second fixed current value for asecond predetermined time duration.

Other embodiments of the methods also include controlling theelectrotransport current in a predetermined profile, wherein thepredetermined profile comprises a ramp over a predetermined timeduration beginning at a first current value and ending at a secondcurrent value.

In some embodiments of the methods disclosed herein, the first fixedcurrent value is 4 mA and the first predetermined time duration is 1hour while the second fixed current value is 2 mA and the secondpredetermined time duration is 3 hours and the predetermined totalrun-time is 4 hours.

Other embodiments of the methods disclosed herein further comprisesdetecting if the electrotransport current reaches a minimum level ofcurrent within an initial period after switching on the device andswitching off the electrotransport current if the electrotransportcurrent does not reach the minimum level of current within the initialperiod.

In certain other embodiments the method further includes the step ofswitching on the device one or more times until a battery of the deviceis depleted.

Other embodiments further comprises the step of controlling theelectrotransport current in a predetermined profile, wherein thepredetermined profile is selected based on a characteristic of theanimal body surface.

In some other embodiments the method further comprises controlling theelectrotransport current in a predetermined profile, wherein thepredetermined profile is selected based on a characteristic of thetherapeutic agent.

In other embodiments of the methods the programming of the controller ischanged subsequent to manufacture of the drug delivery device to adaptto a user of the device.

In certain other embodiments the methods further includes the steps ofprogramming the controller to drive the electrotransport current throughthe animal body surface in a first predetermined profile and changingthe programming of the controller to drive the electrotransport currentthrough the animal body surface in a second predetermined profile.

In certain other embodiments of the methods the programming of thecontroller is changed subsequent to manufacture of the drug deliverydevice to adapt to a user of the device.

Other embodiments of the methods further comprises the step of adjustingthe electrotransport current to account for a change in a resistance ofthe animal body surface.

In certain other embodiments, the methods further comprises the step ofadjusting the electrotransport current to account for a change in aresistance of the animal body surface.

In certain other embodiments, the method further comprises the step ofprogramming the controller to slowly drain the PWM power supply at theend of dosing of the therapeutic agent.

In other embodiments of the invention, a drug delivery device fordriving an electrotransport current through an animal body surface isdisclosed wherein the device comprising a patch having two electrodesand one or more reservoirs storing a therapeutic agent. The one or morereservoirs is adapted to release the therapeutic agent through theanimal body surface when the one or more reservoirs are positioned overthe electrodes to form an electrical path for the electrotransportcurrent traveling from one of the electrodes to the other of theelectrodes. The device further comprises a controllable power supply forapplying an output voltage across the animal body surface and drivingthe electrotransport current through the animal body surface. The devicealso comprises a controller programmed to generate one or moreinterrupts at predetermined intervals, turn off the controllable powersupply when the one or more interrupts are generated, drive theelectrotransport current through the animal body surface in apredetermined profile, determine a present value of the electrotransportcurrent and a representative value of a target electrotransport current,and control the controllable power supply at least based on the presentvalue and the dynamic value representative of the targetelectrotransport current.

In certain other embodiments of the device, the controller controls thecontrollable power supply using a linear regulator. In otherembodiments, the patch and the power supply are integrated.

In certain embodiments of the device, the voltage regulator is aninverse single ended primary inductor converter (SEPIC) voltageregulator while in other embodiments the voltage regulator is a standardbuck converter voltage regulator. In other embodiments, the voltageregulator is a standard boost converter voltage regulator. In someembodiments, the voltage regulator is a buck-boost converter voltageregulator.

In certain other embodiments, the device further comprises alight-emitting diode (LED) for providing a visual indication to indicatethat the device is active.

In other embodiments, the predetermined profile of the electrotransportcurrent comprises a fixed current value for a predetermined timeduration. In other embodiments, the predetermined profile of theelectrotransport current comprises a first fixed current value for afirst predetermined time duration and a ramp of increasing or decreasingcurrent values for a second predetermined time duration.

In other embodiments of the device, the predetermined profile of theelectrotransport current comprises a first fixed current value for afirst predetermined time duration and a second fixed current value for asecond predetermined time duration.

In certain other embodiments of the device, the controller is furtherprogrammed to adjust the electrotransport current to account for achange in a resistance of the animal body surface. In certain otherembodiments, the controller is further programmed to adjust the outputvoltage to account for a change in a resistance of the animal bodysurface.

In certain other embodiments of the device, the potential safety issueis detected during operation of the device if a battery voltage is belowa minimum voltage, the minimum voltage being a voltage below which thecontroller may not function properly.

In other embodiments of the device, the potential safety issue isdetected during operation of the device if the electrotransport currentis higher than a maximum current for a first predefined time duration.

In some embodiments of the device, the potential safety issue isdetected during operation of the device if the electrotransport currentis lower than a minimum current for a second predefined time durationwhile in other embodiments, the potential safety issue is detectedduring operation of the device if the output voltage is higher than amaximum voltage for a predefined time duration.

One skilled in the art will appreciate further features and advantagesof the present invention based on the above-described exemplaryembodiments. Accordingly, the present invention is not to be limited bywhat has been particularly shown and described, except as indicated bythe appended claims.

While the methods, systems and apparatuses of the present invention havebeen particularly shown and described with reference to the exemplaryembodiments thereof, those of ordinary skill in the art will understandthat various changes may be made in the form and details herein withoutdeparting from the spirit and scope of the present invention. Thoseskilled in the art will recognize, or be able to ascertain using no morethan routine experimentation, numerous equivalents to the specificprocedures described herein. Such equivalents are considered to bewithin the scope of the present invention and are covered by theappended claims.

1. In a drug delivery device, a method of driving an electrotransportcurrent through an animal body surface using a controller of the deviceto deliver at least a portion of a therapeutic agent, the methodcomprising: driving the electrotransport current through electrodes ofthe device and through the animal body surface using a controllablepower supply of the device; determining a present value of theelectrotransport current; determining a dynamic value representative ofa target electrotransport current, the dynamic value determined based onthe target electrotransport current, a resistance value of a senseresistor used to detect the electrotransport current flowing between theelectrodes, a value of a bandgap voltage associated with the controller,and a fixed voltage value; and controlling the controllable power supplyusing the controller at least based on the present value of theelectrotransport current and the dynamic value representative of thetarget electrotransport current.
 2. The method of claim 1, wherein thecontroller controls the controllable power supply using a linearregulator.
 3. The method of claim 1, wherein the controller controls thecontrollable power supply using a switching regulator.
 4. The method ofclaim 2, wherein the switching regulator performs pulse width modulation(PWM) and the controllable power supply is a PWM power supply.
 5. Themethod of claim 4, further comprising: controlling a duty cycle of thePWM power supply using the controller at least based on the presentvalue of the electrotransport current and the dynamic valuerepresentative of the target electrotransport current.
 6. The method ofclaim 4, further comprising: controlling a duty cycle of the PWM powersupply using the controller based on a comparison between the presentvalue of the electrotransport current and the dynamic valuerepresentative of the target electrotransport current.
 7. The method ofclaim 4, further comprising: determining a present value of an outputvoltage applied across the animal body surface; determining a dynamicvalue representative of the target output voltage; making a comparisonbetween the present value of the output voltage and the dynamic valuerepresentative of the target output voltage; and controlling a dutycycle of the PWM power supply using the PWM controller based on thecomparison.
 8. The method of claim 7, wherein controlling the duty cycleof the PWM power supply further comprises: determining that the presentvalue of the output voltage is greater than the dynamic valuerepresentative of the target output voltage based on the comparison; andreducing the duty cycle of the PWM power supply by one step withoutperforming an electrotransport current correction.
 9. The method ofclaim 7, wherein controlling the duty cycle of the PWM power supplyfurther comprises: determining that the present value of the outputvoltage is less than or equal to the dynamic value representative of thetarget output voltage based on the comparison; and performing anelectrotransport current correction.
 10. The method of claim 9, whereinperforming the electrotransport current correction comprises: making asecond comparison between the present value of the electrotransportcurrent and the dynamic value representative of the targetelectrotransport current; determining that the present value of theelectrotransport current is greater than the dynamic valuerepresentative of the target electrotransport current based on thesecond comparison; and reducing the duty cycle of the PWM power supplyby one step.
 11. The method of claim 9, wherein performing theelectrotransport current correction comprises: making a secondcomparison between the present value of the electrotransport current andthe dynamic value representative of the target electrotransport current;determining that the present value of the electrotransport current isequal to the dynamic value representative of the target electrotransportcurrent based on the second comparison; and maintaining the duty cycleof the PWM power supply at its present step.
 12. The method of claim 9,wherein performing the electrotransport current correction comprises:making a second comparison between the present value of theelectrotransport current and the dynamic value representative of thetarget electrotransport current; determining that the present value ofthe electrotransport current is less than the dynamic valuerepresentative of the target electrotransport current based on thesecond comparison; and increasing the duty cycle of the PWM power supplyby one step.
 13. The method of claim 1, wherein an output voltageapplied across the animal body surface is maintained below a maximumvalue irrespective of changes in a resistance of the animal body surfaceto avoid burning the animal body surface.
 14. The method of claim 1,further comprising: detecting if there is a minimum level of energy in abattery of the device; and driving the electrotransport current throughthe animal body surface only if the battery has the minimum level ofenergy.
 15. The method of claim 1, further comprising: shutting down thedevice upon detecting a potential safety issue; and providing anindication that the device has been shut down.
 16. The method of claim15, wherein the potential safety issue is detected during operation ofthe device if a battery voltage is below a minimum voltage for apredefined time duration.
 17. The method of claim 15, wherein thepotential safety issue is detected during operation of the device if theelectrotransport current is higher than a maximum current for a firstpredefined time duration.
 18. The method of claim 15, wherein thepotential safety issue is detected during operation of the device if theelectrotransport current is lower than a minimum current for a secondpredefined time duration.
 19. The method of claim 15, wherein thepotential safety issue is detected during operation of the device if anoutput voltage applied across the animal body surface is higher than amaximum voltage for a predefined time duration.
 20. The method of claim1, further comprising: immediately after turning on the drug deliverydevice, applying an output voltage across the animal body surface for apredefined time duration without controlling the power supply.
 21. Themethod of claim 1, further comprising: controlling the electrotransportcurrent in a predetermined profile, wherein the predetermined profile isa fixed current value for a predetermined time duration, the fixedcurrent value based on one or more characteristics of the animal bodysurface, the animal body, and/or the therapeutic agent.
 22. The methodof claim 1, further comprising: detecting if the electrotransportcurrent reaches a minimum level of current within an initial periodafter switching on the device; and switching off the electrotransportcurrent if the electrotransport current does not reach the minimum levelof current within the initial period.
 23. The method of claim 22,further comprising: switching on the device one or more times until abattery of the device is depleted.
 24. The method of claim 1, furthercomprising: controlling the electrotransport current in a predeterminedprofile, wherein the predetermined profile is selected based on acharacteristic of the animal body surface.
 25. The method of claim 1,further comprising: controlling the electrotransport current in apredetermined profile, wherein the predetermined profile is selectedbased on a characteristic of the therapeutic agent.
 26. The method ofclaim 1, further comprising: programming the controller to drive theelectrotransport current through the animal body surface in a firstpredetermined profile; and changing the programming of the controller todrive the electrotransport current through the animal body surface in asecond predetermined profile.
 27. The method of claim 1, furthercomprising: programming the controller to slowly drain a power supply ofthe device at the end of dosing of the therapeutic agent. 28.-51.(canceled)
 52. The method of claim 1, wherein the therapeutic agentcomprises, sumatriptan succinate.
 53. One or more computer readablemedia storing instructions executable by a processing unit for drivingan electrotransport current through an animal body surface using acontroller to deliver at least a portion of a therapeutic agent, themedia comprising instructions for: driving the electrotransport currentthrough electrodes and through the animal body surface using acontrollable power supply; determining a present value of theelectrotransport current; determining a dynamic value representative ofa target electrotransport current, the dynamic value determined based onthe target electrotransport current, a resistance value of a senseresistor used to detect the electrotransport current flowing between theelectrodes, a value of a bandgap voltage associated with the controller,and a fixed voltage value; and controlling the controllable power supplyusing the controller at least based on the present value of theelectrotransport current and the dynamic value representative of thetarget electrotransport current.
 54. The method of claim 1, wherein thedynamic value representative of the target electrotransport current isdetermined based at least on the target electrotransport current and anoperational characteristic of a power supply that varies duringoperation of the power supply.
 55. The method of claim 54, wherein theoperational characteristic of the power supply is a variable outputvoltage of the power supply.
 56. The method of claim 54, wherein thedynamic value representative of the target electrotransport current isdetermined based at least on a reference voltage at an analog-to-digitalconverter that varies during operation of the power supply.